Esters of prostacyclin-type compounds

ABSTRACT

Acyl-substituted phenyl esters of prostacyclin-type compounds, for example the 4-acetylphenyl ester of prostacyclin (PGI 2 ) illustrated by the formula ##STR1## and including esters of the isomeric 6-hydroxy-PGI 2  and 6-keto-PGF 1 α compounds, said esters having pharmacological activity. Processes for preparing them and the appropriate intermediates are disclosed.

The present application is a divisional application of Ser. No. 048,496, filed 14 June 1979; which in turn is a divisional application of Ser. No. 933,329, filed 14 Aug. 1978, now issued as U.S. Pat. No. 4,180,657, on 25 Dec. 1979.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,180,657, issued 25 Dec. 1979. 

We claim:
 1. An acid ester of a 6a-carba prostacyclin analog of the formula ##STR2## wherein L₁ is (1) --(CH₂)_(n) -- wherein n is one to 5, inclusive,(2) --(CH₂)_(p) -- wherein p is 2, 3, or 4, or (3) --(CH₂)_(v) --CH═CH-- wherein v is 1, 2, or 3, wherein M₃ is ##STR3## wherein Q is oxo, α-H:β-H, α-OH:β-R₄, or α-R₄ :β-OH, wherein R₄ is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R₁ alkyl of one to 4 carbon atoms with the proviso that when R₁ is tert-butyl the group ##STR4## is in the 4-position, wherein R₃ is ##STR5## wherein R₅ and R₆ are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R₅ and R₆ is fluoro only when the other is hydrogen or fluoro; and the further proviso that neither R₅ nor R₆ is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C_(j) H_(2j) wherein C_(j) H_(2j) is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR₅ R₆ -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms; inclusive, fluoro, chloro, trifluoromethyl, or --OR₇ -- wherein R₇ is alkyl of one to 4 carbon atoms, inclusive and s is zero, one, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different. wherein R₁₂ is ##STR6## wherein X is (1) trans--CH═CH--(2) cis--CH═CH-- (3) --C.tbd.C-- or (4) --CH₂ CH₂ --. 